The present invention relates to mass spectrometry, and more particularly relates to a system and method for improving quantitation accuracy and mass assignment accuracy for time-of-flight mass spectrometers using a signal offset.
In the field of mass spectrometry, and particularly with regard to atmospheric pressure ion sources (such as Electrospray, Atmospheric Pressure Chemical Ionization (APCI), and Atmospheric Pressure Matrix-Assisted Laser Desorption Ionization (AP MALDI)), there is an increasing demand for more accurate determination of the empirical formulas of compounds that are introduced and ionized using such systems. For example, in Proteomics research, in which the structure and composition of large and complex protein molecules are studied, mass assignment accuracies on the order of 1 to 2 parts per million (ppm) may be required for correct identification. This high level of mass assignment accuracy can be currently achieved using Time-Of-Flight mass spectrometers (TOF MS) that can attain mass resolution levels of greater than ten thousand.
In addition to the demand for high mass assignment accuracy, in a given analysis there may be a need to accurately measure the heights of individual mass peaks in order to assess the relative abundance of different analytes or to precisely determine ratios of different isotopes within a sample.
In TOF MS systems, ions having different mass-to-charge ratios travel through a drift tube at different speeds and reach a detector at the end of the drift tube in a series of narrow xe2x80x9cpacketsxe2x80x9d, each packet containing ions of a specific mass-to-charge ratio (hereinafter simply called xe2x80x9cmassxe2x80x9d). The distribution of ions in time within the packet is translated by the detector and its associated electronics into a mass peak, i.e., data that represent ion number or intensity vs. time or, equivalently, mass. The time (mass) distribution may be approximately Gaussian. Individual packets of ions may be received extremely close together in time, necessitating fast detector systems for detecting and measuring the packets rapidly in order to generate clearly defined peaks centered at specific masses. The resolution of a measurement may be defined as the mass value at peak center divided by the width of the peak at half maximum, for example. The mass accuracy of a measurement is inversely related to the peak width; any widening of the peaks usually will adversely affect the accuracy of determination of the mass corresponding to the peak. In particular, the peaks may widen to the point that neighboring mass peaks partially or completely overlap, making accurate mass assignment extremely difficult.
The present invention provides a method of processing signals generated at a detector of a mass spectrometer in which an offset is applied to the signals prior to signal conversion. In a first processing mode, an offset is applied to the signals to improve quantitation accuracy, and in a second mode an offset of opposite polarity is applied to the signals to improve resolution and mass assignment.
Additionally, in one embodiment, the present invention provides an apparatus for processing signals generated at the detector of a mass spectrometer that comprises an offset generator for generating a signal offset voltage, a summing amplifier having a first input coupled to the detector for receiving signals generated at the detector, a second input coupled to the offset generator for receiving the signal offset voltage, and an output. The summing amplifier adds the signal offset voltage to detector signals and produces an output that represents a sum voltage thereof.